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Isocyanides as key intermediates and magic reactants have been widely applied in organic reactions for direct access to a broad spectrum of remarkable organic compounds. Although the history of these magical compounds dates back more than 100 years, it still has been drawing widespread attention of chemists who confirmed their versatility and effectiveness. Because of their wide spectrum of pharmacological, industrial and synthetic applications, many reactions with the utilization of isocyanides are reported in the literature. In this context, Iranian scientist played a significant role in the growth of isocyanides chemistry. The present review article covers literature from the period starting from 2010 onward and encompasses new synthetic routes and organic transformation involving isocyanides by Iranian researchers. During this period, a diverse range of isocyanide-based multi-component reactions (I-MCRs) has been reported such as a new modification of Ugi, post-Ugi, Passerini and Groebke-Blackburn-Bienayme condensation reactions, isocyanide-based [1 + 4] cycloaddition reactions, isocyanide-acetylene-based MCRs, isocyanide and Meldrum's acid-based MCRs, several unexpected reactions besides green mediums and novel catalytic systems for the synthesis of diverse kinds of pharmaceutically and industrially remarkable heterocyclic and linear organic compounds. This review also emphasizes the neoteric applications of I-MCR for the synthesis of valuable peptide and pseudopeptide scaffolds, enzyme immobilization and functionalization of materials with tailorable properties that can play important roles in the plethora of applications.